From Beyond The Rainbow Somewhere

NANOTECHNOLOGY

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Part of what makes graphene so fantastically useful is its amazing thinness – it’s just one atom thick.

Scientists have now found hundreds of other materials that are equally thin, providing a wide selection of new materials with perhaps as much potential as graphene.

The team analysed data in open resources including the Crystallography Open Database, looking for materials with structural similarities to graphene with the help of a custom computer program.

They were looking for materials with strong chemical bonds along one plane – the 2D atom layer – and relatively weak non-chemical action along the perpendicular plane. It’s this combination that lets us peel sheets of graphene from graphite.

Starting off with a pool of over 100,000 crystal structures, the team from the École Polytechnique Fédérale de Lausanne in Switzerland was able to narrow down the selection to 1,825 compounds with the potential to form sheets just a single atom thick.

“Two-dimensional materials provide opportunities to venture into largely unexplored regions of the materials space,” the researchers explain in their study.

“On the one hand, their ultimate thinness makes them extremely promising for applications in electronics. On the other, the physical properties of monolayers often change dramatically from those of their parent 3D materials, providing a new degree of freedom for applications while also unveiling novel physics.”

In the case of graphene and graphite, graphite is held together by a relatively weak electrostatic interaction known as a van der Waals force. Usually this is strong enough to keep the material together, but it does allow graphene to be extracted.

Whether or not that will also be true for the 1,825 materials identified here remains to be seen, but they have been shown to be structurally similar in terms of atom locations and their chemical bonds. A few of the structures have never been seen before.

Based on calculations run on 258 of the less complex chemicals in the final list, the researchers found that 166 turned out to be semiconductors with a variety of voltages. Meanwhile, 92 materials were identified as metallic, with another 56 likely to have unusual magnetic properties.

Even if just a small subsection of these new materials end up functioning like graphene does, that gives us a lot more options for creating materials for specific purposes in electronics and other areas. The next step is to test how these compounds work in both sheet form and in tightly packed layers.

What we do know thanks to this advanced database search is that these materials might just be exfoliable – able to be peeled into super-thin layers just like graphene. It’s going to be exciting to see what happens next with the materials on this list.

“The materials identified are classified into groups of easily or potentially exfoliable compounds, showing that only a very small fraction of possible 2D materials has been considered up to now,” conclude the researchers.

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Researchers in the Netherlands are hoping to move vaccine therapy from the lab to inside the body.

Stimulating or enhancing someone’s own immune system to fight cancer is not a new concept but scientists are taking it one step further by using nanoscience and computer simulations to improve existing treatments.

Immunotherapy drugs are specifically designed to help the immune system respond to cancerous cells, something that it doesn’t naturally do. That’s because cancer cells are essentially the body’s own cells gone rogue and the immune system is programmed not to target native cells.

Now, a new computer simulation that mimics the body’s response when exposed to certain immunotherapy drugs could speed up their development by eliminating any dud ideas at an earlier stage.

Scientists on the EU-funded MODICELL project have developed prototype software that can trial potential recipes for drugs by using a kind of graphic interface called reactive animation to demonstrate the body’s expected response.

With the information gained from the simulation, the scientists can decide whether to pursue developing a potential drug or to go back to the drawing board, without wasting valuable time and resources.

‘We wanted to develop a computerised approach that will allow us to simulate and to make predictions regarding immune responses that could be used to improve therapies against cancer or in-organ transplantations,’ said Dr Nuno Andrade of St. Anna Children’s Cancer Research Institute, Austria, who managed the project.

To improve the accuracy of the simulations, the researchers first of all conducted real-life experiments in the laboratory and collected extensive biological information from published literature.

Computer scientists worked in the lab together with biologists to better understand the behaviour of the immune system, and used the knowledge gained to develop the computer simulation.

‘There is no way that we can keep doing science without computerised approaches.’

Dr Andrade says this type of collaboration is likely to continue. ‘Biology is such a complex science. There is no way that we can keep doing science without computerised approaches.’

Vaccines

One drug-based approach to immunotherapy that is currently used to treat cancer is vaccine therapy. Today this involves taking a blood sample from a patient and mixing it with molecules found on the tumour called antigens. A substance known as an adjuvant is then added to help the immune cells in the blood sample respond to these antigens, and these activated immune cells are injected back into the patient’s body.

However, because this takes place in a lab, the process is cumbersome and time-consuming. The EU-funded PRECIOUS project is developing a novel nano-sized vaccine containing nanoparticles packed with both antigens and an adjuvant, which can be injected into the patient to stimulate the immune response inside the body.

Professor Carl Figdor of Radboud University Medical Center, the Netherlands, who leads the project, said that this couldn’t happen without nanoparticles. ‘These particles are so small that you can inject them directly into the bloodstream without harming the patient. If you were to use bigger particles or bigger molecules then you would have all kinds of difficulties, perhaps small blood vessels would clog.’

Advantages include reduced wait times for the patient and a stable vaccine that is not so heavily affected by the individual health concerns of each patient.

‘Here we are going to have a product that is much more stable and of a constant quality, and is cheaper in the end because it can be used in a much wider way for a lot of patients,’ said Prof. Figdor.

Large scale

The idea is to find an efficient process for creating these nanoparticles en masse so that nanovaccines can be manufactured on a large scale. The PRECIOUS team will test their nanoparticles for safety in humans and if successful will move up to trials involving 500 people.

‘There is a lot of gain because you make one product that you can use for a lot of patients, rather than having to take blood from each patient, making an individual vaccine, which is labour intensive and expensive,’ said Prof. Figdor.

Nano-sized particles are also being used to improve a kind of cancer therapy called photodynamic therapy (PDT). PDT involves a photoactive drug, called a photosensitiser, which, when introduced into the body, acts like a ticking bomb – it is safe until it is activated by contact with a particular wavelength of light and then it reacts with oxygen to form a chemical that kills the cells.

It’s not fully understood how or why, but PDT is also thought to activate the immune system to attack the cancer.

Expel

However, the problem with the photosensitisers currently in use is that they stick to all the body’s cells, not only cancer cells. Healthy cells will expel the drug after two to four days, whereas cancer cells find the photosensitisers much more difficult to remove. Patients returning after two to four days are exposed to the type of light which activates the photoactive drug, killing the cancer cells.

Now, scientists on the KILLCANCER project, funded by the EU’s European Research Council, plan to reduce this waiting period to just a couple of hours by developing an approach where small nanobodies – fragments of antibodies – are bound chemically to the photosensitiser. These actively target cancerous cells, but not healthy cells.

‘We expect that we can more efficiently reach cancer cells compared to traditional antibodies,’ said Dr Sabrina Oliveira of Utrecht University, the Netherlands, who leads the work. The project is also investigating how PDT interacts with the immune system response.

The next goal for the research is to progress from mouse studies to larger animals like cats and dogs. In the near future, Dr Oliveira will start working with veterinary centres to offer PDT as a therapy for cats with oral cancer, and can then use the resulting data to produce a body of evidence supporting nanobody-targeted PDT.

The issue

Improving immunotherapy treatments isn’t just about developing better drugs, it’s also about manufacturing those treatments on a large scale so they can be used in the wider population.

To support this, the EU has allocated more than €1.5 billion to research into industrial leadership in the areas of nanotechnologies, advanced materials, biotechnology and advanced manufacturing and processing between 2018 and 2020.

The work includes addressing the regulatory framework and developing an environment that enables high-quality healthcare for Europeans. Nanomedicines that are developed in the EU for use in tumour-targeted treatment strategies are produced at an industrial level that respects the highest possible quality standards.

In 2013, the European Technology Platform on Nanomedicine (ETPN) set up Nano World Cancer Day, which this year takes place on 2 February and is supported by the EU-funded ENATRANS project. There will be simultaneous events in 10 countries to demonstrate the disruptive nanomedicine-based innovations that are being developed to beat cancer.

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Recently, European scientists bombarded tattooed corpses with X-rays from a particle accelerator. While it could have been a scene for an upcoming goth body horror movie, it was actually a study meant to benefit living humans with tattoos. This grisly experiment helped European nanoparticle researchers understand how tattoo ink travels in human bodies over time.

In a study published in the journal Scientific Reports on Tuesday, a team of French and German researchers reports that nanoparticles found in some tattoo inks can migrate away from the skin — and accumulate in lymph nodes.

Some ink particles can travel to the lymph nodes, like those under the ears.

First, the scientists took samples of lymph nodes and skin from four tattooed donor cadavers and one un-tattooed control cadaver. Then, they examined the skin and lymph nodes to see whether the pigments present in the skin were also in the lymph nodes. If that were the case, it would suggest that particles in the ink had indeed migrated through the lymphatic system to the lymph nodes, which filter lymph, the fluid that carries white blood cells through the body to fight infections.

Sure enough, they did find particles in the nodes, confirming their long-held suspicion that pigment particles accumulate there.

“We found a broad range of tattoo pigment particles with up to several micrometers in size in human skin but only smaller (nano)particles transported to the lymph nodes,” write the study’s authors. They suspect that the larger particles — those up to a micrometer across — can’t travel through the lymphatic system. Which is a good thing, because they found that just the small particles had caused the tattooed donors’ lymph nodes to become enlarged.

In particular, the researchers found elevated levels of titanium dioxide — a white tattoo ink pigment that’s added to other pigments to create various color shades — in the skin and lymph nodes of tattooed donors but not in the control sample.

Scientists found that some pigments in tattoo ink can migrate from the skin into the lymph nodes.

Unsettling as it may be for people with tattoos to learn that their ink isn’t staying put, it’s actually not that surprising that tattoo pigment particles can be found in the lymphatic system. When foreign matter like tattoo ink is traumatically inserted into the body, this system’s action kicks into high gear in its attempt to expel invaders.

Until now, this kind of research had been challenging to conduct. The scientists needed to test actual biological tissues, but that presented a dilemma.

“The animal experiments which would be necessary to address these toxicological issues were rated unethical because tattoos are applied as a matter of choice and lack medical necessity, similar to cosmetics,” the study’s authors write.

Admittedly, this is a small sample size, so these findings are far from being the final word on the matter, and this paper definitely doesn’t support some advocates’ argument that tattoo ink can cause cancer. But it does confirm that tattoo pigments can both travel in the body and accumulate in lymph nodes, which could be worrisome.

“In future experiments we will also look into the pigment and heavy metal burden of other, more distant internal organs and tissues in order to track any possible biodistribution of tattoo ink ingredients throughout the body,” write the authors.

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The quantum dots can be used for bioimaging and measuring intracellular temperature

Using mango leaves to synthesise fluorescent graphene quantum dots (nanocrystals of semiconductor material), researchers from the Indian Institute of Technology (IIT) Bombay have been able to produce cheap probes for bioimaging and for intracellular temperature sensing.

Unlike the currently used dyes, quantum dots synthesised from mango leaves are biocompatible, have excellent photostability and show no cellular toxicity. The results were published in the journal ACS Sustainable Chemistry & Engineering.

Green route

To synthesise quantum dots, the researchers cut mango leaves into tiny pieces and froze them using liquid nitrogen. The frozen leaves were crushed into powder and dipped in alcohol. The extract was centrifuged and the supernatant evaporated in an evaporator and then heated in a microwave for five minutes to get a fine powder.

Using mice fibroblast cells, a team led by Rohit Srivastava from the Department of Biosciences and Bioengineering at IIT Bombay evaluated the potential of quantum dots for bioimaging and temperature-sensing applications. In mice cell in vitro studies, the graphene quantum dots were able to get into the cells easily without destroying the integrity, viability and multiplication of the cells. The quantum dots get into the cytoplasm of the cell.

The quantum dots, 2-8 nanometre in size, were found to emit red luminescence when excited by UV light. “Even when the excitation wavelength was 300-500 nanometre, the emission from the quantum dots was at 680 nanometre. The quantum dots exhibited excitation-independent emission,” says Mukeshchand Thakur from the Department of Biosciences and Bioengineering at IIT Bombay, one of the authors of the paper.

The quantum dots have smaller and larger fluorescent units. When the excitation is at lower wavelength, the smaller units transfer energy to the larger units and there is red emission. And when the excitation is at higher wavelength, the red emission comes directly from the larger units, thus remaining excitation-independent.

The quantum dots that Mukesh Kumar Kumawat (left) and Rohit Srivastava have fabricated can be used for bioimaging.

Nanothermometer

“Since the quantum dots get into the cytoplasm of the cell, the graphene quantum dots can be used for cell cytoplasm labelling applications,” says Mukesh Kumar Kumawat from the Department of Biosciences and Bioengineering, IIT Bombay and the first author of the paper.

The quantum dots found inside the cells showed intense florescence at 25 degree C. As the temperature rises to 45 degree C, the intensity of fluorescence tends to decrease.

As a result, the researchers found up to 95% reduction in fluorescence intensity when the temperature was increased by 20 degree C. “So quantum dots can be used for detecting temperature variation in the intracellular environment,” says Thakur.

“The graphene quantum dots can be used as a nanothermometre. Besides measuring intracellular temperature increase, they can be used for measuring temperature increase in cancer cells and when there is inflammation,” says Prof. Srivastava. “We are seeing interest by companies making imaging probes. There is also interest to use it as a temperature probe.”

“Since the quantum dots emit red light, they can be used for making organic light-emitting diodes as well,” says Kumawat.

Researchers have achieved a major turning point in the quest for efficient desalination by announcing the invention of a graphene-oxide membrane that sieves salt right out of seawater.

At this stage, the technique is still limited to the lab, but it’s a demonstration of how we could one day quickly and easily turn one of our most abundant resources, seawater, into one of our most scarce – clean drinking water.

The team, led by Rahul Nair from the University of Manchester in the UK, has shown that the sieve can efficiently filter out salts, and now the next step is to test this against existing desalination membranes.

“Realisation of scalable membranes with uniform pore size down to atomic scale is a significant step forward and will open new possibilities for improving the efficiency of desalination technology,” says Nair.

“This is the first clear-cut experiment in this regime. We also demonstrate that there are realistic possibilities to scale up the described approach and mass produce graphene-based membranes with required sieve sizes.”

Graphene-oxide membranes have long been considered a promising candidate for filtration and desalination, but although many teams have developed membranes that could sieve large particles out of water, getting rid of salt requires even smaller sieves that scientists have struggled to create.

One big issue is that, when graphene-oxide membranes are immersed in water, they swell up, allowing salt particles to flow through the engorged pores.

The Manchester team overcame this by building walls of epoxy resin on either side of the graphene oxide membrane, stopping it from swelling up in water.

This allowed them to precisely control the pore size in the membrane, creating holes tiny enough to filter out all common salts from seawater.

The key to this is the fact that when common salts are dissolved in water, they form a ‘shell’ of water molecules around themselves.

“The size of the shell of water around the salt is larger than the channel size, so it cannot go through.”

Not only did this leave seawater fresh to drink, it also made the water molecules flow way faster through the membrane barrier, which is perfect for use in desalination.

“When the capillary size is around one nanometre, which is very close to the size of the water molecule, those molecules form a nice interconnected arrangement like a train,” Nair explained to Rincon.

“That makes the movement of water faster: if you push harder on one side, the molecules all move on the other side because of the hydrogen bonds between them. You can only get that situation if the channel size is very small.”

There are already several major desalination plants around the world using polymer-based membranes to filter out salt, but the process is still largely inefficient and expensive, so finding a way to make it quicker, cheaper, and easier is a huge goal for researchers.

Thanks to climate change, seawater is something we’re going to have plenty of in the future – Greenland’s coastal ice caps which have already passed the point of no return are predicted to increase sea levels by around 3.8 cm (1.5 inches) by 2100, and if the entire Greenland Ice Sheet melts, future generations will be facing oceans up to 7.3 metres (24 feet) higher.

But at the same time, clean drinking water is still incredibly hard to come by in many parts of the world – the UN predicts that by 2025, 14 percent of the world’s population will encounter water scarcity. And many of those countries won’t be able to afford large-scale desalination plants.

The researchers are now hoping that the graphene-based sieve might be as effective as large plants on the small scale, so it’s easier to roll out.

Graphene oxide is also a lot easier and cheaper to make in the lab than single-layers of graphene, which means the technology will be affordable and easy to produce.

“The selective separation of water molecules from ions by physical restriction of interlayer spacing opens the door to the synthesis of inexpensive membranes for desalination,” Ram Devanathan from the Pacific Northwest National Laboratory, who wasn’t involved in the research, wrote in an accompanyingNature News and Views article.

“The ultimate goal is to create a filtration device that will produce potable water from seawater or wastewater with minimal energy input.”

He added that the next step will be to test how durable the membranes are when used over long periods of time, and how often they need to be replaced.

Tiny carbon dots have, for the first time, been applied to intracellular imaging and tracking of drug delivery involving various optical and vibrational spectroscopic-based techniques such as fluorescence, Raman, and hyperspectral imaging. Researchers have demonstrated, for the first time, that photo luminescent carbon nanoparticles can exhibit reversible switching of their optical properties in cancer cells.

Tiny carbon dots have, for the first time, been applied to intracellular imaging and tracking of drug delivery involving various optical and vibrational spectroscopic-based techniques such as fluorescence, Raman, and hyperspectral imaging. Researchers from the University of Illinois at Urbana-Champaign have demonstrated, for the first time, that photo luminescent carbon nanoparticles can exhibit reversible switching of their optical properties in cancer cells.

“One of the major advantages of these agents are their strong intrinsic optical sensitivity without the need for any additional dye/fluorophore and with no photo-bleaching issues associated with it,” explained Dipanjan Pan, an assistant professor of bioengineering and the leader of the study. “Using some elegant nanoscale surface chemistry, we created a molecular ‘masking’ pathway to turn off the fluorescence and then selectively remove the mask leading to regaining the brightness.

“Using carbon dots for illuminating human cells is not new. In fact, my laboratories, and several other groups around world, have shown that these tiny dots represent a unique class of luminescent materials with excellent biocompatibility, degradability, and relatively facile access to large-scale synthesis in comparison to other popular luminescent materials such as quantum dots,” added Pan.

And, the entire process of is highly controlled and can be observed in living cells as they reported in the group’s study, “Macromolecularly ‘Caged’ Carbon Nanoparticles for Intracellular Trafficking via Switchable Photoluminescence,” appearing in the Journal of the American Chemical Society.

“We can apply this technique for intracellular trafficking by means of switchable photo-luminescence in mammalian cells in vitro, wherein the endocytic membrane-abundant anionic amphiphilic molecules participates in the ‘de-caging’ process,” stated Pan. “The carbon dots, each measuring less than 50 nanometers in diameter, are derived from agave nectar and are highly luminescent. The in situ nanoscale chemical exchange further probed into the mechanistic understanding of the origin of carbon luminescence and indicated that it is primarily a surface phenomenon.

“This can be reversibly turned on and off by a simple counter-ionic nanoscale chemistry,” Pan said. “These results can become the basis for new and interesting designs for carbon-based materials for intracellular imaging probing cellular function and to study other biological processes.”

Professor Mike Kelly at Cambridge University’s Centre for Advanced Photonics and Electronics has stunned a budding nanotechnology industry by saying that structures with a diameter of three nanometres or less cannot be mass-produced. “This statement raises a major question concerning the billions of dollars that are poured into nanotechnology each year in the hope that the latest technology developed in the lab can make the transition to a manufactured product on the market,” according to Phys Org.

What’s the Big Idea?

Nanotechnology is built on the ability to control and manipulate matter at the atomic and molecular level and has already had far reaching applications including helping drugs to be delivered into patients’ bodies, improving food packaging and increasing the efficiency of solar panels. It is a budding industry that, given recent success in the laboratory—the 2010 Nobel Prize was given to two scientists for their experiments with graphene, an extremely tough one-atom-think nanostructure—holds large commercial potential.

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Acne, a scourge of adolescence, may be about to meet its ultra high-tech match. By using a combination of ultrasound, gold-covered particles and lasers, researchers have developed a targeted therapy that could potentially lessen the frequency and intensity of breakouts, relieving acne sufferers the discomfort and stress of dealing with severe and recurring pimples.

The particles are delivered into the sebaceous gland by the ultrasound, and are heated by the laser. The heat deactivates the gland.

Acne, a scourge of adolescence, may be about to meet its ultra high-tech match. By using a combination of ultrasound, gold-covered particles and lasers, researchers from UC Santa Barbara and the private medical device company Sebacia have developed a targeted therapy that could potentially lessen the frequency and intensity of breakouts, relieving acne sufferers the discomfort and stress of dealing with severe and recurring pimples.

“Through this unique collaboration, we have essentially established the foundation of a novel therapy,” said Samir Mitragotri, professor of chemical engineering at UCSB.

Pimples form when follicles get blocked by sebum, an oily, waxy substance secreted by sebaceous glands located adjacent to the follicle. Excretion of sebum is a natural process and functions to lubricate and waterproof the skin. Occasionally, however, the openings of the follicles (pores) get blocked, typically by bits of hair, skin, dirt or other debris mixed in with the sebum. Overproduction of sebum is also a problem, which can be caused by hormones or medications. Changes in the skin, such as its thickening during puberty, can also contribute to follicle blockage. Whatever the cause, the accumulating sebum harbors bacteria, which results in the inflammation and local infection that we call acne.

The new technology builds on Mitragotri’s specialties in targeted therapy and transdermal drug delivery. Using low-frequency ultrasound, the therapy pushes gold-coated silica particles through the follicle into the sebaceous glands. Postdoctoral research associate Byeong Hee Hwang, now an assistant professor at Incheon National University, conducted research at UCSB.

“The unique thing about these particles is that when you shine a laser on them, they efficiently convert light into heat via a process called surface plasmon resonance,” said Mitragotri. This also marks the first time ultrasound, which has been proved for years to deliver drugs through the skin, has been used to deliver the particles into humans.

These silica and gold particles are exceedingly tiny — about a hundredth of the width of a human hair — but they are key to the therapy. Once the particles are deposited in the target areas, lasers are aimed at them and, because the gold shells are designed specifically to interact with the near-infrared wavelengths of the lasers, the light becomes heat. The heated particles essentially cause deactivation of the sebaceous glands. The sebum, pore-blocking substances and particles are excreted normally.

“If you deactivate these overproducing glands, you’re basically treating the root cause of the acne,” said Mitragotri.

According to the research, which is published in the Journal of Controlled Release, this protocol would have several benefits over conventional treatments. Called selective photothermolysis, the method does not irritate or dry the skin’s surface. In addition, it poses no risk of resistance or long-term side effects that can occur with antibiotics or other systemic treatments.

“It’s highly local but highly potent as well,” Mitragotri said of the treatment. “I think this would be beneficial in addressing the concerns regarding other, conventional treatments.” According to Mitragotri, this photothermolysis method is particularly suited to patients with advanced, severe or difficult-to-treat acne. The research has gone from concept to clinical trials in a relatively short amount of time. However, other more long-term elements of this therapy have yet to be studied, such as the extent of follicular damage, if any; what the most effective and beneficial parameters of this treatment may be; and what contraindications exist.

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Scientists at UC Santa Barbara have created the most high-tech solution to teenage anxiety yet: a treatment for acne that uses a combination of ultrasound, gold-covered nanoparticles, and lasers.

The research is unique because it has created what amounts to a therapeutic regimen that works in three distinct steps. And rather than treating the symptoms of acne, like medications that can dry the face and cause extreme sensitivity to sunlight, the nanotechnology treatment attacks acne at its source.

First, golden nanoparticles, whose width is less than one-hundredth that of a human hair, are applied to the skin. Then, ultrasound pushes the particles through the hair follicle into the sebaceous gland, which releases the oily substance responsible for causing acne. Finally, a laser is shined on the skin that turns the gold particles into heat, disabling the glands

Published in the Journal of Controlled Release, researchers explain that the treatment would not cause the skin to dry out since the blocking of follicles would simply be prevented:

“Called selective photothermolysis, the method does not irritate or dry the skin’s surface. In addition, it poses no risk of resistance or long-term side effects that can occur with antibiotics or other systemic treatments.”

The extremely small size of the golden particles that penetrate hair follicles is the key to the treatment, an advance brought about by the development of nanotechnology, or the ability to control physical elements at the nanoscale. The future for this technology is promising, particularly regarding the treatment of medical conditions located in the brain.

An obstacle called the blood-brain barrier currently prevents most medications from treating the brain directly, but nanotechnology can overcome those obstacles. More interesting still is the technology’s potential to aid learning by carrying encoded information directly to memory centers in the brain. It’s a technology currently beyond the horizon, to be sure, but Nicholas Negroponte explains how it would work in his Big Think interview:

“The best way to interact with the brain is from the inside, from the bloodstream. Because if you inject tiny robots into the bloodstream, they can get very close to all the cells and nerves and things in your brain, really close. So if you want to input information or read information, you do it through the bloodstream. So by extension … you could in theory load Shakespeare into your bloodstream and as the little robots get to the various parts of the brain, they deposit little pieces of Shakespeare or little pieces of French if you want to learn how to speak French.”